Modeling freedom from progression for standard-risk medulloblastoma : A mathematical tumor control model with multiple modes of failure
Brodin, N. Patrik ; Vogelius, Ivan R. ; Björk-Eriksson, Thomas LU ; Munck Af Rosenschöld, Per LU
and Bentzen, Søren M.
(2013)
In International Journal of Radiation Oncology, Biology, Physics
87(2).
p.422-429
- Abstract
Purpose As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data. Methods and Materials Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom... (More)
Purpose As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data. Methods and Materials Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom from progression (FFP) was estimated by Monte Carlo sampling over the statistical uncertainty in input data. Results The estimated 5-year FFP (95% confidence intervals [CI]) for craniospinal doses of 15, 18, 24, and 36 Gy while maintaining 54 Gy to the posterior fossa was 77% (95% CI, 70%-81%), 78% (95% CI, 73%-81%), 79% (95% CI, 76%-82%), and 80% (95% CI, 77%-84%) respectively. The uncertainty in FFP was considerably larger for craniospinal doses below 18 Gy, reflecting the lack of data in the lower dose range. Conclusions Estimates of tumor control and time-to-progression for standard-risk MB provides a data-driven setting for hypothesis generation or power calculations for prospective trials, taking the uncertainties into account. The presented methods can also be applied to incorporate further risk-stratification for example based on molecular biomarkers, when the necessary data become available.
(Less)
- author
- Brodin, N. Patrik
; Vogelius, Ivan R.
; Björk-Eriksson, Thomas
LU
; Munck Af Rosenschöld, Per
LU
and Bentzen, Søren M.
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- International Journal of Radiation Oncology, Biology, Physics
- volume
- 87
- issue
- 2
- pages
- 8 pages
- publisher
- Elsevier
- external identifiers
-
- wos:000324310500034
- scopus:84882874068
- pmid:23910711
- ISSN
- 0360-3016
- DOI
- 10.1016/j.ijrobp.2013.06.008
- language
- English
- LU publication?
- yes
- id
- 2c5b6717-92db-4c3a-8ec9-db4efb5a4a6d (old id 4102093)
- date added to LUP
- 2016-04-01 11:03:01
- date last changed
- 2023-08-08 11:33:43
@article{2c5b6717-92db-4c3a-8ec9-db4efb5a4a6d,
abstract = {{<p>Purpose As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data. Methods and Materials Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom from progression (FFP) was estimated by Monte Carlo sampling over the statistical uncertainty in input data. Results The estimated 5-year FFP (95% confidence intervals [CI]) for craniospinal doses of 15, 18, 24, and 36 Gy while maintaining 54 Gy to the posterior fossa was 77% (95% CI, 70%-81%), 78% (95% CI, 73%-81%), 79% (95% CI, 76%-82%), and 80% (95% CI, 77%-84%) respectively. The uncertainty in FFP was considerably larger for craniospinal doses below 18 Gy, reflecting the lack of data in the lower dose range. Conclusions Estimates of tumor control and time-to-progression for standard-risk MB provides a data-driven setting for hypothesis generation or power calculations for prospective trials, taking the uncertainties into account. The presented methods can also be applied to incorporate further risk-stratification for example based on molecular biomarkers, when the necessary data become available.</p>}},
author = {{Brodin, N. Patrik and Vogelius, Ivan R. and Björk-Eriksson, Thomas and Munck Af Rosenschöld, Per and Bentzen, Søren M.}},
issn = {{0360-3016}},
language = {{eng}},
number = {{2}},
pages = {{422--429}},
publisher = {{Elsevier}},
series = {{International Journal of Radiation Oncology, Biology, Physics}},
title = {{Modeling freedom from progression for standard-risk medulloblastoma : A mathematical tumor control model with multiple modes of failure}},
url = {{http://dx.doi.org/10.1016/j.ijrobp.2013.06.008}},
doi = {{10.1016/j.ijrobp.2013.06.008}},
volume = {{87}},
year = {{2013}},
}